Urine has a rich and longstanding clinical history as a source for monitoring developing conditions and remains an integral component of a health examination.[1] Well over one hundred tests can be performed to indicate conditions as diverse as pregnancy,[2] diabetes,[3] kidney diseases,[4] metabolic disorders and others. Inspired by the elegant physiology of the renal system—which has evolved the capacity to selectively filter liters of blood within minutes to remove byproducts of biological processes—we recently developed a class of protease-sensitive nanoparticles, called ‘synthetic biomarkers’, that in response to dysregulated protease activity at the sites of disease, release reporters into the circulation that are then concentrated into the host urine for noninvasive monitoring, using multiplexing techniques such as mass spectrometry for detection.[6] Dysregulation of proteases in cancer has important consequences in cell signaling and helps drive cancer cell proliferation, invasion, angiogenesis, avoidance of apoptosis, and metastasis. In murine models of liver fibrosis and cancer, synthetic urinary biomarkers removed the need for invasive monitoring of solid organs by core biopsies, and significantly improved early stage detection of cancer compared to a tumor-secreted blood biomarker.